Proposing Restoration of Circadian Rhythm as an Approach to Treat Sarcopenia
Circadian rhythm becomes disrupted with age, and a growing body of evidence points to this form of dysfunction as a contribution to many aspects of aging. The fine details of how and why circadian regulation of cell and tissue activity runs awry are complex and incompletely understood. Different circadian clocks operate in different parts of the body, communicate with one another, but fall out of synchronization in old individuals. Then cell types also change in different ways in their response to circadian signaling. While there is considerable interest in manipulating circadian mechanisms to restore better function in later life, little progress has been made towards working therapies. This paper is illustrative of present work; arguments are made as to which directions to take in the development of therapies to restore circadian activity, but a great deal remains to be accomplished.
Sarcopenia, characterized by the age-related decline in skeletal muscle mass, strength, and function, is associated with high healthcare costs and significant health risks, including falls, fractures, functional decline, and mortality. Despite its prevalence and extensive research, there are currently no Food and Drug Administration (FDA)-approved drugs to modify its course, likely due to an incomplete understanding of its underlying mechanisms. Recent evidence highlights two key factors in sarcopenia development: (1) Disrupted circadian rhythms affecting pathways such as protein remodeling, insulin resistance, and mitochondrial function; (2) systemic chronic low-grade inflammation (SCLGI).
This review focuses on circadian rhythm regulators implicated in skeletal muscle deterioration, examining their roles, potential interactions, and the impact of circadian disruption on sarcopenia progression. Additionally, we explore how clock genes reciprocally influence the inflammatory profile, which is crucial for developing treatment strategies to mitigate the detrimental effects of sarcopenia. We also examine factors that influence the clock and have the potential to restore circadian rhythm mechanisms that are deregulated in sarcopenia. Drawing from these insights, strategies aimed at restoring circadian synchrony and resolving inflammation are proposed as a novel therapeutic approach to effectively mitigate the manifestations of sarcopenia.